Reacciones de hipersensibilidad a alglucosidasa alfa en enfermedad de Pompe: dos casos de desensibilización exitosa / Hypersensitivity reactions to alglucosidase alfa in Pompe disease: two cases of successful desensitization

La enfermedad de Pompe es un desorden neuromuscular autosómico recesivo de baja prevalencia, causado por la deficiencia total o parcial de la enzima alfa glucosidasa ácida (GAA), cuya única terapia de reemplazo enzimático disponible es la alglucosidasa alfa recombinante. Las reacciones adversas asociadas a la infusión se presentan con frecuencia. Se reportan dos casos de desensibilización exitosa con alglucosidasa alfa utilizando protocolos con dosis meta de 20 mg/kg, administrados quincenalmente; el primero de ellos, en una niña con historia de reacción adversa grave a los 15 meses de edad, en quien se utilizó un esquema con una dilución inicial de 1/10.000.000 de 28 pasos y una duración total de 13,1 horas. En el segundo caso, la paciente tuvo una reacción adversa grave a los 4 años de edad, se utilizó el protocolo de 22 pasos, concentración inicial de 1/1.000.000 y duración total de 7,2 horas. Se concluye que en pacientes con enfermedad de Pompe que presentan reacciones adversas durante la terapia de reemplazo enzimático, es posible realizar la desensibilización cada dos semanas con la dosis estándar de 20 mg/kg de forma exitosa, y progresivamente lograr la administración usual de la infusión

Pompe disease is a low prevalence autosomal recessive neuromuscular disorder, caused by total or partial deficiency of the acid alpha-glucosidase (GAA) enzyme, and its only available enzyme replacement therapy is the recombinant alglucosidase alfa. Infusion-associated adverse reactions occur frequently. Two cases of successful desensitization with alglucosidase alfa using protocols with a target dose of 20 mg/kg administered biweekly are reported; the first was a girl who had a history of serious adverse reaction at the age of 15 months, and undergone to a scheme with an initial dilution of 1/10,000,000 with 28 steps and a total duration of 13.1 hours. In the second case, the patient had a severe adverse reaction at the age of 4 years, a 22-step protocol was used with an initial concentration of 1/1,000,000 and a total duration of 7.2 hours. In conclusion, in patients with Pompe disease who presented adverse reactions during enzyme replacement therapy with alglucosidase alfa, it is possible to perform desensitization every two weeks with the standard dose of 20 mg/kg, and progressively achieve the usual administration of the infusion

Actividad hipoglucemiante in vitro de los polisacáridos digeridos de Nostoc sphaericum Vaucher ex Bornet & Flahault (cushuro) / In vitro hypoglycemic activity of polysaccharides digested from Nostoc sphaericum Vaucher ex Bornet & Flahault (cushuro)

Objetivo: Evaluar el potencial inhibitorio de las enzimas α-amilasa y α-glucosidasa, así como la inhibición de la difusión de la glucosa, por los polisacáridos aislados de Nostoc Sphaericum Vaucher ex Bornet & Flahault tratados mediante digestión gastrointestinal simulada a nivel in vitro. Materiales y métodos: Los polisacáridos obtenidos de microalga fueron purificados y tratados mediante digestibilidad gastrointestinal in vitro, con la finalidad de simular su digestión. Se evaluó la actividad hipoglucemiante mediante los métodos de inhibición de la α-glucosidasa, α-amilasa y la difusión de la glucosa de los polisacáridos digeridos, comparados con el medicamento acarbosa. Resultados: Los resultados mostraron que la concentración de 50 mg/mL de polisacáridos digeridos disminuye en un 85,26 % la difusión de la glucosa a nivel in vitro. La concentración inhibitoria (CI50) de la enzima α-glucosidasa fue de 314,23 ± 4,87 mg/mL y la enzima α-amilasa 113,59 ± 3,10 mg/mL. Conclusiones: Los polisacáridos de Nostoc sphaericum tratados mediante digestión gastrointestinal in vitro, mostraron capacidad de inhibir las enzimas α-amilasa, α-glucosidasa y la difusión de glucosa; motivo por el cual la especie sería considerado promisoria para un posible tratamiento coadyuvante de la diabetes tipo 2

Objective: To evaluate the inhibitory potential of the α-amylase and α-glucosidase enzymes, as well as the inhibition of glucose diffusion, using polysaccharides isolated from Nostoc sphaericum Vaucher ex Bornet & Flahault and treated by in vitro simulated gastrointestinal digestion. Materials and methods: The polysaccharides obtained from the microalga were purified and treated through in vitro gastrointestinal digestibility in order to simulate digestion. The hypoglycemic activity was evaluated by methods such as the inhibition of α-glucosidase and α-amylase, and glucose diffusion of the digested polysaccharides, and compared with the medication acarbose. Results: The results showed that the concentration of 50 mg/mL of digested polysaccharides decreases by 85.26 % the spread of in vitro glucose. The inhibitory concentration (IC50) of the α-glucosidase enzyme was 314.23 ± 4.87 mg/mL and that of the α-amylase enzyme was 113.59 ± 3.10 mg/mL. Conclusions: Nostoc sphaericum polysaccharides treated by in vitro gastrointestinal digestion showed the ability to inhibit the α-amylase and α-glucosidase enzymes, and glucose diffusion. Therefore, this species would be considered promising for a possible adjuvant treatment of type 2 diabetes

Detecting multiple lysosomal enzymes in dried blood spots by tandem mass spectrometry / 中华检验医学杂志

Objective Establish a method for measuring the activities of Galactocerebrosidase (GALC), α-Glucosidase(GAA), α-Galactosidase (GLA) and α-L-Iduronidase (IDUA) in dried blood spots specimen by tandem mass spectrometry ( MS/MS ).Methods A total of 2175 dried blood spot samples forinborn errors of metabolism in neonatalscreening center of Shanghai Xinhua hospital were collected in July and November, 2013.And twenty dried blood spot samples from patients withlysosomalstorage disorders( LSDs) of Shanghai Xin Hua Hospital were collected from September 2012 to January 2014.The extraction of DBS was incubated with enzyme substrates and internal standards.After liquid-liquid and solid-phase extraction, the extraction solution was dried under nitrogen and reconstituted.Then enzyme reaction products and internal standards were analyzed by MS/MS.Linearity, precision, accuracy and the limit of detection were evaluated.2175 dried blood spot samples were detected to establish the normal reference range for the activities of four enzymes according to 0.5th to 99.5th percentiles.20 specimens from patients withLSDs were detected to verify the reference range inclinical judgment.Results The intraassay and interassay precisions ranged from 1.7%to 11.8%, and the intraassay and interassay accuracies ranged from 85%to 115%.The linear coefficients for measured concentration of enzyme products/internal standards and theoretical concentration were 0.997-0.999.The limits of detection forGALC, GAA, GLA and GLA were 0.03 μmol/(L· h), 0.09 μmol/(L· h), 0.12 μmol/(L· h) and 0.16 μmol/(L· h) .The normal reference values for GALC, GAA, GLA and GLAwere 0.51-8.51μmol( L· h) ,1.99-22.22μmol/( L· h),1.68-41.59 μmol/(L· h) and 2.36-19.21 μmol/(L· h).The enzymes of 20 patients with LSDs were remarkably decreased compared to the normal range.The Krabbe, Pompe, Fabry, MPSⅠpatients can be effectively detected by this MS/MS method.Conclusions A MS/MS method for measuring GALC, GAA, GLA and IDUA enzyme activities in DBShas been established.

Clinical, pathological and molecular genetic studies on a pedigree with late-onset Pompe's disease complicated with cerebral vascular diseases / 中华神经科杂志

Objective To report a pedigree with late-onset Pompe' s disease complicated with cerebral vascular diseases as to summarize their clinical,pathological and molecular genetic characteristics.Methods We investigated the clinical and pathological data of the two affected siblings with late-onset Pompe' s disease complicated with cerebral vascular diseases.All the 5 members of this pedigree accepted the GAA gene analysis.ResultsBoth affected siblings had progressive pelvic girdle muscle weakness from young adult age,and recently developed vertigo and ataxia.Brain imaging of them revealed multiple cerebral hemorrhage,infarction and diffuse ischemic white matter lesions.The brother had multiple aneurysms and stenoses of cerebral arteries revealed by brain CTA.However,his sister was only found to have multi-beaded stenoses of cerebral arteries.The muscle pathology of the brother showed typical vacuolar degeneration and glycogen storage in muscle fibers. The GAA enzyme activity of 2 siblings were dramatically lower than normal.A heterozygous 19 bp-deletion (c.1388-c.1406,exon 9) were found in GAA gene in the 2 siblings and their healthy mother. Conclusions Cerebrovascular involvement should be a special phenotype of Pompe' s disease.A novel heterozygous mutation c.1388del19 in GAA gene was found in this pedigree,but the relationship between the mutation and the rare clinical phenotype needs further study.

Impact of infection on the secretory capacity of the male accessory glands

INTRODUCTION: Studies that compare the impact of different infectious entities of the male reproductive tract (MRT) on the male accessory gland function are controversial. MATERIAL AND METHODS: Semen analyses of 71 patients with proven infections of the MRT were compared with the results of 40 healthy non-infected volunteers. Patients were divided into 3 groups according to their diagnosis: chronic prostatitis NIH type II (n = 38), chronic epididymitis (n = 12), and chronic urethritis (n = 21). RESULTS: The bacteriological analysis revealed 9 different types of microorganisms, considered to be the etiological agents, isolated in different secretions, including: urine, expressed prostatic secretions, semen and urethral smears: E. Coli (n = 20), Klebsiella (n = 2), Proteus spp. (n = 1), Enterococcus (n = 20), Staphylococcus spp. (n = 1), M. tuberculosis (n = 2), N. gonorrhea (n = 8), Chlamydia tr. (n = 16) and, Ureaplasma urealyticum (n = 1). The infection group had significantly (p < 0.05) lower: semen volume, alpha-glucosidase, fructose, and zinc in seminal plasma and, higher pH than the control group. None of these parameters was sufficiently accurate in the ROC analysis to discriminate between infected and non-infected men. CONCLUSION: Proven bacterial infections of the MRT impact negatively on all the accessory gland function parameters evaluated in semen, suggesting impairment of the secretory capacity of the epididymis, seminal vesicles and prostate. These findings were associated with an infectious related significant increase of semen pH. None of the semen parameters evaluated can be suggested as a diagnostic tool for infection.

Clinical improvement in a case of atypical infantile onset Pompe disease with enzyme replacement therapy / 소아과

Pompe disease is a genetic disorder caused by a deficiency of acid alpha-glucosidase (GAA). Infantile onset Pompe disease is uniformly lethal. Affected infants generally present in the first few months of life with hypotonia, generalized muscle weakness, and a hypertrophic cardiomyopathy, which is rapidly followed by death, usually by the age of one. The late-onset form is characterized less severe symptoms and prognosis. Therapy for Pompe disease is intended to directly address the underlying metabolic defect via intravenous infusions of recombinant human GAA to replace the missing enzyme. We report a case of atypical infantile-onset Pompe disease that presented symptoms in infancy but had less severe clinical manifestations and improved after GAA enzyme replacement (Myozyme(R), Genzyme Co., MA, USA) therapy. It is very important that pediatricians become aware of signs and symptoms of Pompe disease, such as a nasal voice or a waddling gait at an early stage so that these patients can benefit from appropriate GAA replacement therapy as soon as possible.